Identification of genetic polymorphisms associated with risk for pulmonary hypertension in sickle cell disease

Allison E. Ashley-Koch, Laine Elliott, Melanie E. Kail, Laura M. De Castro, Jude Jonassaint, Terry L. Jackson, Jennifer Price, Kenneth Ataga, Marc C. Levesque, J. Brice Weinberg, Eugene P. Orringer, Ann Collins, Jeffery M. Vance, Marilyn J. Telen

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

Up to 30% of adult patients with sickle cell disease (SCD) will develop pulmonary hypertension (pHTN), a complication associated with significant morbidity and mortality. To identify genetic factors that contribute to risk for pHTN in SCD, we performed association analysis with 297 single nucleotide polymorphisms (SNPs) in 49 candidate genes in patients with sickle cell anemia (Hb SS) who had been screened for pHTN by echocardiography (n = 111). Evidence of association was primarily identified for genes in the TGFβ superfamily, including activin A re-ceptor, type ll - Iike 1 (ACVRL1), bone morphogenetic protein receptor 2 (BMPR2), and bone morphogenetic protein 6 (BMP6). The association of pHTN with ACVRL1 and BMPR2 corroborates the previous association of these genes with primary pHTN. Moreover, genes in the TGFβ pathway have been independently implicated in risk for several sickle cell complications, suggesting that this gene pathway is important in overall sickle cell pathophysiology. Genetic variation in the (β-1 adrenergic receptor (ADRB1) was also associated with pHTN in our dataset. A multiple regression model, which included age and baseline hemoglobin as covariates, retained SNPs in ACVRL1, BMP6, and ADRB1 as independently contributing to pHTN risk. These findings may offer new promise for identifying patients at risk for pHTN, developing new therapeutic targets, and reducing the occurrence of this life-threatening SCD complication

Original languageEnglish (US)
Pages (from-to)5721-5726
Number of pages6
JournalBlood
Volume111
Issue number12
DOIs
StatePublished - Jun 15 2008

Fingerprint

Sickle Cell Anemia
Genetic Polymorphisms
Polymorphism
Pulmonary Hypertension
Genes
Bone Morphogenetic Protein 6
Bone Morphogenetic Protein Receptors
Bone Morphogenetic Protein 2
Nucleotides
Echocardiography
Single Nucleotide Polymorphism
Adrenergic Receptors
Hemoglobins
Morbidity
Mortality

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Ashley-Koch, A. E., Elliott, L., Kail, M. E., De Castro, L. M., Jonassaint, J., Jackson, T. L., ... Telen, M. J. (2008). Identification of genetic polymorphisms associated with risk for pulmonary hypertension in sickle cell disease. Blood, 111(12), 5721-5726. https://doi.org/10.1182/blood-2007-02-074849

Identification of genetic polymorphisms associated with risk for pulmonary hypertension in sickle cell disease. / Ashley-Koch, Allison E.; Elliott, Laine; Kail, Melanie E.; De Castro, Laura M.; Jonassaint, Jude; Jackson, Terry L.; Price, Jennifer; Ataga, Kenneth; Levesque, Marc C.; Weinberg, J. Brice; Orringer, Eugene P.; Collins, Ann; Vance, Jeffery M.; Telen, Marilyn J.

In: Blood, Vol. 111, No. 12, 15.06.2008, p. 5721-5726.

Research output: Contribution to journalArticle

Ashley-Koch, AE, Elliott, L, Kail, ME, De Castro, LM, Jonassaint, J, Jackson, TL, Price, J, Ataga, K, Levesque, MC, Weinberg, JB, Orringer, EP, Collins, A, Vance, JM & Telen, MJ 2008, 'Identification of genetic polymorphisms associated with risk for pulmonary hypertension in sickle cell disease', Blood, vol. 111, no. 12, pp. 5721-5726. https://doi.org/10.1182/blood-2007-02-074849
Ashley-Koch AE, Elliott L, Kail ME, De Castro LM, Jonassaint J, Jackson TL et al. Identification of genetic polymorphisms associated with risk for pulmonary hypertension in sickle cell disease. Blood. 2008 Jun 15;111(12):5721-5726. https://doi.org/10.1182/blood-2007-02-074849
Ashley-Koch, Allison E. ; Elliott, Laine ; Kail, Melanie E. ; De Castro, Laura M. ; Jonassaint, Jude ; Jackson, Terry L. ; Price, Jennifer ; Ataga, Kenneth ; Levesque, Marc C. ; Weinberg, J. Brice ; Orringer, Eugene P. ; Collins, Ann ; Vance, Jeffery M. ; Telen, Marilyn J. / Identification of genetic polymorphisms associated with risk for pulmonary hypertension in sickle cell disease. In: Blood. 2008 ; Vol. 111, No. 12. pp. 5721-5726.
@article{695f113a8d1d4dea8f1a5181df3baeac,
title = "Identification of genetic polymorphisms associated with risk for pulmonary hypertension in sickle cell disease",
abstract = "Up to 30{\%} of adult patients with sickle cell disease (SCD) will develop pulmonary hypertension (pHTN), a complication associated with significant morbidity and mortality. To identify genetic factors that contribute to risk for pHTN in SCD, we performed association analysis with 297 single nucleotide polymorphisms (SNPs) in 49 candidate genes in patients with sickle cell anemia (Hb SS) who had been screened for pHTN by echocardiography (n = 111). Evidence of association was primarily identified for genes in the TGFβ superfamily, including activin A re-ceptor, type ll - Iike 1 (ACVRL1), bone morphogenetic protein receptor 2 (BMPR2), and bone morphogenetic protein 6 (BMP6). The association of pHTN with ACVRL1 and BMPR2 corroborates the previous association of these genes with primary pHTN. Moreover, genes in the TGFβ pathway have been independently implicated in risk for several sickle cell complications, suggesting that this gene pathway is important in overall sickle cell pathophysiology. Genetic variation in the (β-1 adrenergic receptor (ADRB1) was also associated with pHTN in our dataset. A multiple regression model, which included age and baseline hemoglobin as covariates, retained SNPs in ACVRL1, BMP6, and ADRB1 as independently contributing to pHTN risk. These findings may offer new promise for identifying patients at risk for pHTN, developing new therapeutic targets, and reducing the occurrence of this life-threatening SCD complication",
author = "Ashley-Koch, {Allison E.} and Laine Elliott and Kail, {Melanie E.} and {De Castro}, {Laura M.} and Jude Jonassaint and Jackson, {Terry L.} and Jennifer Price and Kenneth Ataga and Levesque, {Marc C.} and Weinberg, {J. Brice} and Orringer, {Eugene P.} and Ann Collins and Vance, {Jeffery M.} and Telen, {Marilyn J.}",
year = "2008",
month = "6",
day = "15",
doi = "10.1182/blood-2007-02-074849",
language = "English (US)",
volume = "111",
pages = "5721--5726",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "12",

}

TY - JOUR

T1 - Identification of genetic polymorphisms associated with risk for pulmonary hypertension in sickle cell disease

AU - Ashley-Koch, Allison E.

AU - Elliott, Laine

AU - Kail, Melanie E.

AU - De Castro, Laura M.

AU - Jonassaint, Jude

AU - Jackson, Terry L.

AU - Price, Jennifer

AU - Ataga, Kenneth

AU - Levesque, Marc C.

AU - Weinberg, J. Brice

AU - Orringer, Eugene P.

AU - Collins, Ann

AU - Vance, Jeffery M.

AU - Telen, Marilyn J.

PY - 2008/6/15

Y1 - 2008/6/15

N2 - Up to 30% of adult patients with sickle cell disease (SCD) will develop pulmonary hypertension (pHTN), a complication associated with significant morbidity and mortality. To identify genetic factors that contribute to risk for pHTN in SCD, we performed association analysis with 297 single nucleotide polymorphisms (SNPs) in 49 candidate genes in patients with sickle cell anemia (Hb SS) who had been screened for pHTN by echocardiography (n = 111). Evidence of association was primarily identified for genes in the TGFβ superfamily, including activin A re-ceptor, type ll - Iike 1 (ACVRL1), bone morphogenetic protein receptor 2 (BMPR2), and bone morphogenetic protein 6 (BMP6). The association of pHTN with ACVRL1 and BMPR2 corroborates the previous association of these genes with primary pHTN. Moreover, genes in the TGFβ pathway have been independently implicated in risk for several sickle cell complications, suggesting that this gene pathway is important in overall sickle cell pathophysiology. Genetic variation in the (β-1 adrenergic receptor (ADRB1) was also associated with pHTN in our dataset. A multiple regression model, which included age and baseline hemoglobin as covariates, retained SNPs in ACVRL1, BMP6, and ADRB1 as independently contributing to pHTN risk. These findings may offer new promise for identifying patients at risk for pHTN, developing new therapeutic targets, and reducing the occurrence of this life-threatening SCD complication

AB - Up to 30% of adult patients with sickle cell disease (SCD) will develop pulmonary hypertension (pHTN), a complication associated with significant morbidity and mortality. To identify genetic factors that contribute to risk for pHTN in SCD, we performed association analysis with 297 single nucleotide polymorphisms (SNPs) in 49 candidate genes in patients with sickle cell anemia (Hb SS) who had been screened for pHTN by echocardiography (n = 111). Evidence of association was primarily identified for genes in the TGFβ superfamily, including activin A re-ceptor, type ll - Iike 1 (ACVRL1), bone morphogenetic protein receptor 2 (BMPR2), and bone morphogenetic protein 6 (BMP6). The association of pHTN with ACVRL1 and BMPR2 corroborates the previous association of these genes with primary pHTN. Moreover, genes in the TGFβ pathway have been independently implicated in risk for several sickle cell complications, suggesting that this gene pathway is important in overall sickle cell pathophysiology. Genetic variation in the (β-1 adrenergic receptor (ADRB1) was also associated with pHTN in our dataset. A multiple regression model, which included age and baseline hemoglobin as covariates, retained SNPs in ACVRL1, BMP6, and ADRB1 as independently contributing to pHTN risk. These findings may offer new promise for identifying patients at risk for pHTN, developing new therapeutic targets, and reducing the occurrence of this life-threatening SCD complication

UR - http://www.scopus.com/inward/record.url?scp=47049113837&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=47049113837&partnerID=8YFLogxK

U2 - 10.1182/blood-2007-02-074849

DO - 10.1182/blood-2007-02-074849

M3 - Article

VL - 111

SP - 5721

EP - 5726

JO - Blood

JF - Blood

SN - 0006-4971

IS - 12

ER -